Update on Hepatitis C: Trials & Treatment and Protesting Gilead
Hello everyone, here we are heading into September, where does the time go?
During the next few weeks I will be busy working on a family project, the kids need nana to babysit, I can't wait! Once I get my short people under control the blog and website should get updated. On second thought, not sure that is likely to happen, if not, see you in a few weeks....
Last month the New York City Hepatitis C Task Force, along with Tracey Swan from the Treatment Action Group (TAG) offered a training seminar to help patients understand more about participating in a clinical trial. The program provided an overview of new terminology, SVR rates according to genotype using current and future HCV therapies under development. View the slide presentation, here, highlighting the following:
Update on Hepatitis C: Trials & Treatment
OVERVIEW
• New terms
• HCV in the US
• Trial participation
• When to treat
• Curing HCV: from interferon to DAAs
• DAAs
• Cure rates, by HCV genotype
• What’s here now, and what’s coming
• Treat now, or wait?
• What matters most?
In case you missed it, TAG's 2014 Pipeline Report is available, here.
Of Interest:
79 Study Locations
Recruiting Sofosbuvir/GS-5816 Fixed Dose Combination for 12 Weeks in Adults With Chronic HCV Infection
Condition: Hepatitis C Virus Infection
Interventions: Drug: SOF/GS-5816; Drug: Placebo to match SOF/GS-5816
Phase: Phase 3
NCT Number: NCT02201940
Other IDs: GS-US-342-1138, 2014-001683-35
Title Acronym: ASTRAL-1
For additional information visit HCV Advocate News and Pipeline for trial updates;
In The News
Gilead to sell pricey hepatitis C drug in poor countries for fraction of U.S. cost
Ron Leuty
Reporter-San Francisco Business Times
Gilead Sciences Inc. will make its pricey hepatitis C drug Sovaldi available in about 80 poorer countries for less than the cost of a single pill in the United States, according to Bloomberg.
Gilead to sell pricey hepatitis C drug in poor countries for fraction of U.S. cost
Ron Leuty
Reporter-San Francisco Business Times
Gilead Sciences Inc. will make its pricey hepatitis C drug Sovaldi available in about 80 poorer countries for less than the cost of a single pill in the United States, according to Bloomberg.
Gilead executive vice president Gregg Alton told the news agency that a broad licensing deal with a handful of generic drug makers could be completed by mid-September. After winning regulatory approvals in those countries, Sovaldi then could be sold in India, Indonesia, Pakistan and the other countries for $900 for 12 weeks of therapy....
New hepatitis C drugs could stop an epidemic that now claims more lives in the U.S. than AIDS. An estimated 250,000 New Yorkers are living with hepatitis C, a viral infection that can lead to cirrhosis, liver failure and liver cancer. But hepatitis C can be cured with only a few months of treatment by a combination of drugs that includes Gilead’s Sovaldi as the backbone.
Gilead is selling Sovaldi for $1,000 per pill – a price that is causing treatment rationing, according to advocates. “Public and private payers are restricting access to Sovaldi because of cost, and withholding treatment from people until they have serious liver damage. We don’t force HIV-positive people to wait until they have AIDS before treating them. Should people with hepatitis C go without treatment so Gilead can make more profit?,” asked Michael Tikili of Health GAP, a global treatment access advocacy group.
Today healthcare and labor groups protested Gilead at the Baird Healthcare Conference, a prominent investor meeting, demanding that Gilead immediately reduce the price of Sovaldi, and targeting other companies who will be marketing breakthrough HCV drugs before the end of the year. The coalition includes 1199SEIU United Healthcare Workers East – the largest healthcare union in the nation – ACT UP New York, Health GAP, the Treatment Action Group, and VOCAL New York.
“Healthcare isn’t some wild west gold rush, we’re talking about pricing policies that are directly responsible for people dying,” said Matt Curtis, Policy Director at VOCAL New York, an activist group that represents people living with hepatitis C. “Experts have estimated that 12 weeks of Sovaldi costs well under $200 to produce, but because of Gilead’s greed U.S. states are now adopting treatment guidelines that restrict access. A markup of 40,000% doesn’t reflect ‘value’ as Gilead claims, it’s a conscious decision to prey on people desperate for a cure.”
Helen Schaub, New York State Director of Policy and Legislation for 1199SEIU United Healthcare Workers East, noted the impact on the New York State Medicaid budget. “The members of 1199SEIU United Healthcare Workers East always advocate for the best care for their patients, including the estimated 250,000 New Yorkers infected with Hepatitis C,” said Schaub. “They must have access to the treatment they need, including Sovaldi. But at $84,000 per person, this drug could cost New York State billions of dollars. We cannot let Gilead’s outrageous pricing threaten our Medicaid budget and access to healthcare for the 5.8 million New Yorkers who depend on Medicaid services. Gilead must drop the price now.”
“Gilead has ultimately limited access to life-saving drugs – and their own market – with their disgraceful approach to pricing,” said Tracy Swan, Hepatitis/HIV Project Director with the Treatment Action Group. “We know how much it really costs to produce these drugs at a reasonable profit. Other drug makers have a chance to save their drugs from falling into the poisoned well – if you make them affordable, people won’t die, they will be cured.”
Link:
Reducing the cost of new hepatitis C drugs
An index of articles pointing the reader to the current controversy over the high price of Sovaldi.
September Newsletters
Gilead is selling Sovaldi for $1,000 per pill – a price that is causing treatment rationing, according to advocates. “Public and private payers are restricting access to Sovaldi because of cost, and withholding treatment from people until they have serious liver damage. We don’t force HIV-positive people to wait until they have AIDS before treating them. Should people with hepatitis C go without treatment so Gilead can make more profit?,” asked Michael Tikili of Health GAP, a global treatment access advocacy group.
Today healthcare and labor groups protested Gilead at the Baird Healthcare Conference, a prominent investor meeting, demanding that Gilead immediately reduce the price of Sovaldi, and targeting other companies who will be marketing breakthrough HCV drugs before the end of the year. The coalition includes 1199SEIU United Healthcare Workers East – the largest healthcare union in the nation – ACT UP New York, Health GAP, the Treatment Action Group, and VOCAL New York.
“Healthcare isn’t some wild west gold rush, we’re talking about pricing policies that are directly responsible for people dying,” said Matt Curtis, Policy Director at VOCAL New York, an activist group that represents people living with hepatitis C. “Experts have estimated that 12 weeks of Sovaldi costs well under $200 to produce, but because of Gilead’s greed U.S. states are now adopting treatment guidelines that restrict access. A markup of 40,000% doesn’t reflect ‘value’ as Gilead claims, it’s a conscious decision to prey on people desperate for a cure.”
Helen Schaub, New York State Director of Policy and Legislation for 1199SEIU United Healthcare Workers East, noted the impact on the New York State Medicaid budget. “The members of 1199SEIU United Healthcare Workers East always advocate for the best care for their patients, including the estimated 250,000 New Yorkers infected with Hepatitis C,” said Schaub. “They must have access to the treatment they need, including Sovaldi. But at $84,000 per person, this drug could cost New York State billions of dollars. We cannot let Gilead’s outrageous pricing threaten our Medicaid budget and access to healthcare for the 5.8 million New Yorkers who depend on Medicaid services. Gilead must drop the price now.”
“Gilead has ultimately limited access to life-saving drugs – and their own market – with their disgraceful approach to pricing,” said Tracy Swan, Hepatitis/HIV Project Director with the Treatment Action Group. “We know how much it really costs to produce these drugs at a reasonable profit. Other drug makers have a chance to save their drugs from falling into the poisoned well – if you make them affordable, people won’t die, they will be cured.”
Link:
Reducing the cost of new hepatitis C drugs
An index of articles pointing the reader to the current controversy over the high price of Sovaldi.
September Newsletters
Now on with this months edition of HCV Newsletters. Recently, CAP - Caring Ambassadors Program, announced they will be updating part 2; Treatment and Management Approaches, of their popular publication; Hepatitis C Choices Book;2014 5th edition. Check their website for updates, links to each chapter is provided below.....
If you frequent CAP's website, as I do, you may have noticed the site has a new look, with an impressive amount of information. In addition, through NPR’s StoryCorps visitors can now listen to audio featuring patient stories, including two individuals you may know.
Caring Ambassadors Program
The primary goal of the Caring Ambassadors Program is to help individuals with challenging health conditions to become ambassadors for their own health. We are here to help you—that is now and always will be our singular focus.
In this issue
Review of the Most Relevant Research on Hepatitis C
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September Newsletter
In This Issue:
The AASLD/IDSA/IAS–USA Guidelines
Alan Franciscus, Editor-in-Chief
The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA/IAS-USA) recently issued revised guidelines.
In This Issue:
The AASLD/IDSA/IAS–USA Guidelines
Alan Franciscus, Editor-in-Chief
The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA/IAS-USA) recently issued revised guidelines.
Read more...
Alan Franciscus, Editor-in-Chief
This month's column will feature journal articles on two Phase 3 studies of interferon-free therapies as well as a brief overview of HCV drug studies presented at the AIDS 2014 conference held in Melbourne, Australia.
Lucinda K. Porter, RN
This month Lucinda talks about hepatitis C and chronic kidney disease (CKD)encephalopathy, and the fact that HCV may be directly responsible for renal (kidney) injury.
Lucinda K. Porter, RN
Lucinda reviews studies on the changing burden of hepatitis C virus infection in the United States and research on preventing mortality in cirrhotic and genotype 1 infected individuals.
Alan Franciscus, Editor-in-Chief
This month's column will feature journal articles on two Phase 3 studies of interferon-free therapies as well as a brief overview of HCV drug studies presented at the AIDS 2014 conference held in Melbourne, Australia.
Lucinda K. Porter, RN
This month Lucinda talks about hepatitis C and chronic kidney disease (CKD)encephalopathy, and the fact that HCV may be directly responsible for renal (kidney) injury.
Lucinda K. Porter, RN
Lucinda reviews studies on the changing burden of hepatitis C virus infection in the United States and research on preventing mortality in cirrhotic and genotype 1 infected individuals.
Connect With HCV Advocate
Welcome to the new HCV Action website, the home of the UK’s hepatitis C professional community. Browse our tailored resource libraries, view our case study map or find out more information, here.
The HCV Action network brings together health professionals from across the patient pathway, including GPs, specialist nurses, clinicians, drug action teams, public health practitioners, prison healthcare staff and commissioners. We provide resources for commissioners, medical and drug services professionals, promoting good practice in HCV care across the UK.Visit their new website, here.
LATEST NEWS FROM THE HEPATITIS C TRUST
An Evening with Cathal Smyth
3 Sep 14
Nurses London to Paris hep C cycle
27 Aug 14
How to reduce HCV incidence amongst PWID
27 Aug 14
Key Points: NICE draft recommendation for Sofosbuvir
20 Aug 14
Of Interest
Format Video
In this good practice film, HCV Action interviews Jayne Wilkie, Hepatitis C Community Nurse, and Dr Diane Exley from the Brownlow Health Practice in Liverpool. Brownlow Health's unique primary care model of testing, diagnosis and treatment for hepatitis C through a Hepatitis C Community Nurse has led to significant positive outcomes locally. In particular, diagnoses have been increased, do not attends reduced, treatment initiations increased, and the burden has been eased on secondary and tertiary services in Liverpool. Jayne and Diane tell HCV Action about why and how the service was established, as well as detailing how it has developed into a highly successful model of how hepatitis C can be managed in a primary care setting.
The film features Professor Graham Foster (Professor of Hepatology at Queen Mary University of London), Shabana Begum (South Asian Officer at The Hepatitis C Trust), and Imam Yunus Dudhwala (Head of Chaplaincy at Barts Health NHS Trust). It explains why it's so important for the British Pakistani community to understand, prevent and get tested for hepatitis B & C; providing an overview of the viruses, detailing risk factors and providing information on treatment options.
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September News
Scottish Harm Reduction Program Scale-up Lowers Hep C Cases
A comprehensive harm reduction program instituted by the Scottish government has sharply reduced hepatitis C rates among injection drug users.
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September NewsScottish Harm Reduction Program Scale-up Lowers Hep C Cases
A comprehensive harm reduction program instituted by the Scottish government has sharply reduced hepatitis C rates among injection drug users.
Faster, Easier Cures for Hepatitis C
The Food and Drug Administration (FDA) says hepatitis C can be cured, and today's drug therapies are very effective and easier for patients to take.
The Food and Drug Administration (FDA) says hepatitis C can be cured, and today's drug therapies are very effective and easier for patients to take.
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Project Inform believes it is possible to create the first generation free of HIV and hepatitis C within the next decade. To achieve that dream, we focus our work in four areas: drug development, bio-medical prevention, education and health care access.
NVHR Fact Sheet: Why Screen for HCV in an Uncertain Treatment Climate
The current challenges in hepatitis C treatment access have caused some medical providers to be hesitant about screening their patients. The National Viral Hepatitis Roundtable (NVHR) has developed this fact sheet explaining why screening is critical even during this uncertain treatment climate.
The current challenges in hepatitis C treatment access have caused some medical providers to be hesitant about screening their patients. The National Viral Hepatitis Roundtable (NVHR) has developed this fact sheet explaining why screening is critical even during this uncertain treatment climate.
HELP-4-HEP (hepatitis C helpline)
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Healthy You
To Swim or Not to Swim? Safe Swimming Tips for Liver Transplant Recipients
The research team determined that among cases enrolled, liver injuries from herbal and dietary supplements rose to 20% during the study period. While bodybuilding supplements caused prolonged jaundice (median 91 days) in young men, no fatalities or liver transplantations occurred. Death or liver transplantation occurred more frequently among cases of injury from non-bodybuilding supplements, 13%, than from conventional medications, 3%. Liver injury from non-bodybuilding supplements was more common in middle aged women.
Dr. Navarro said, "Our study group is specific to DILIN centers and therefore we cannot conclude that liver injury due to herbals and dietary supplements in on the rise in the U.S. Further population-based study of liver injury due to herbal products and dietary supplements is needed." The authors want to inform the public of potential dangers of using dietary supplements and advise that supplement producers, government agencies, healthcare providers and consumers work together to improve safety.
Source: Wiley
Does Coffee Affect Development of Cholestatic Liver Disorders?
Dr. Kristine Novak
Coffee is considered to be a medically beneficial beverage—consumption has been associated with reductions in metabolic syndrome, cardiovascular disease, and weight gain, as well as total and cause-specific mortality. Furthermore, many studies have reported that coffee consumption reduces the risk of liver diseases such as alcoholic liver disease, cirrhosis, and hepatocellular carcinoma.
Related Link
2014 - Coffee Consumption and Liver Disease
Does Coffee Affect Development of Cholestatic Liver Disorders?
Dr. Kristine Novak
Coffee is considered to be a medically beneficial beverage—consumption has been associated with reductions in metabolic syndrome, cardiovascular disease, and weight gain, as well as total and cause-specific mortality. Furthermore, many studies have reported that coffee consumption reduces the risk of liver diseases such as alcoholic liver disease, cirrhosis, and hepatocellular carcinoma.
Related Link
2014 - Coffee Consumption and Liver Disease
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Liver Disease Quiz: Test Your Medical IQ
Looking for Early Signs of Hepatitis C? We Can Help You Know How
Increasing Rates of Acute Hepatitis C Infection Among Young Americans
By Will Boggs MD
September 03, 2014NEW YORK (Reuters Health) - The incidence of acute hepatitis C infection is rising rapidly among Americans aged 30 years and younger, especially those living in non-urban areas, according to U.S. data.
"Because our study revealed a strong relationship between new infections and injection drug use among youth, we would encourage providers to be on high alert for these risk behaviors in young patients," said senior author Dr. Scott D. Holmberg from the Centers for Disease Control and Prevention in Atlanta, Georgia.
"Assessing their risk can be an important opportunity -- not only for testing but also to provide appropriate therapy or referral to drug-cessation treatment," he told Reuters Health by email.
The number of acute cases of hepatitis C virus (HCV) infection had declined rapidly between 1992 and 2003. But since 2006, there has been a resurgence, especially among younger persons who inject drugs.
Between 2006 and 2012, the agency received reports of 7,169 cases of acute hepatitis C. Nearly half of all cases in 2012 involved people aged 30 years and younger, versus only 36% of cases in 2006, the researchers report in Clinical Infectious Diseases, online August 11.
Thirty of 34 states and territories reporting to CDC reported higher incidence of acute HCV in 2012 compared to 2006 among young persons. Fifteen percent of these states had increases between 100% and 199%, and 50% had increases of at least 200%.
In this age group, the incidence of reported acute HCV infection increased 13% per year in non-urban counties and 5% per year in urban counties. The greatest year-to-year increase occurred from 2010 to 2011, when the increase was 38% in non-urban and 85% in urban counties.
Supplemental case follow-up of 1,202 cases in six jurisdictions revealed that 77% of those newly infected had used injected drugs (57% of these shared needles or syringes and 82% shared other drug preparation equipment).
Among those interviewed, 84% reported having ever used drugs, including marijuana (91%), alcohol (83%), prescription opioids (76%), powder cocaine (71%) and heroin (61%). For the 54% who used both heroin and prescription opioids, heroin use followed the use of prescription opioids by an average 2.4 years.
The researchers note that these reports "grossly underestimate HCV incidence in young persons for many reasons, but mainly because most acute infections are asymptomatic and cannot be detected."
"A comprehensive approach is needed to address the increases in HCV infection among young persons," they conclude. "The early abuse of prescription opioids presents an opportunity to mitigate high-risk behaviors. Possible interventions include provider education to reduce opioid misuse, treatment of drug abuse and addiction, national prescription opioid monitoring, and aggressive early education to mitigate evolution to injection drug use."
"Currently, CDC is supporting demonstration projects in two rural and Appalachian settings to conduct outreach to young people who inject drugs," Dr. Holmberg said. "Our goal is to better understand how to identify these at-risk youth, as well as how to test and appropriately treat them."
"While we've recently seen great advances in hepatitis C treatment, including the availability of new treatments, these new therapies only work if people receive them," Dr. Holmberg said. "The potential of these and other advances depends on our ability to get more people screened and into care.""Testing, specifically, is the first critical step to stemming the toll of death and disease from hepatitis C in this nation," he added. "CDC recommends testing for those known to be at high risk, which includes anyone with a history of injection drug use (other key hepatitis C testing recommendations can be found at http://1.usa.gov/1B8Zj9d). "
Dr. Brian R. Edlin and Emily Winkelstein from the National Development and Research Institutes in New York, who were not involved in the study, recently published an article on the question of whether hepatitis C can be eradicated in the U.S.
"We're at a watershed in this disease now, with the opportunity to end the hepatitis C epidemic within our grasp, but there's a lot that needs to be done to take advantage of the opportunity," Dr. Edlin told Reuters Health by email. "A potentially fatal, lifelong blood-borne viral disease has gone from incurable to curable, which is a historic event in the history of medicine. But the way things are going, it will just move into the forgotten sectors of society, stay there, and continue to spread, until we make a concerted effort to eradicate it."
"Primary care doctors have a terrific opportunity," Dr. Edlin said. "They see patients before they wind up in the emergency room, or jail, or the morgue. Even better, they can organize outreach to young people at risk. Work with the health department, the police, churches and social services to reach out to young people at risk. As doctors, they have a special credibility that others don't. Express concern. Teach. Counsel. Test. And treat."
Winkelstein added, "While I am not a physician, I have heard countless stories from young people who use drugs who have been treated poorly once drug use is discovered or disclosed. More often than not, young people report that physicians shift their dialogue entirely from whatever brought the young person to the physician to a lecture about cessation of all drug use. As a result, young people either stop seeking medical care or don't disclose important health information to in order to avoid backlash."
"Physicians need to find a way to challenge drug-related stigma rather than reinforce it," Winkelstein said. "They must find ways to treat young people with compassion and empathy regardless of their choices around drug use, and seize the opportunity to build trust, provide meaningful education about ways to reduce their risk of getting or transmitting HCV and treat people who are already infected regardless of ongoing use. Physicians can use treatment as a way to continue engagement with young people and prevent reinfection."
Dr. Benjamin P. Linas from Boston University School of Public Health argued that it will be difficult for doctors to have a big impact because young drug users rarely go to the doctor.
"To really stop this spread of infection, we need to focus on substance abuse treatment," he told Reuters Health by email.
"There is a great deal of discussion about the new HCV meds and how we may be able to use them to eradicate HCV," said Dr. Linas, who was not involved in the study. "Maybe we can -- but treatment as prevention cannot work if kids are relapsing to injection drug use and becoming reinfected."
He added, "As a public health/medical community, we need to expand our thinking about HCV beyond the 'boomers.' It was important and appropriate to begin with the recommendation to screen the birth cohort, but it's time to move to the next phase and realize that if we want to really stop new infections, we need to do the very hard work of identifying and engaging HCV-infected active drug users in care, help them stop their drug use, and treat their HCV."
SOURCE
Clin Infect Dis 2014.
Stanford addiction expert: It’s often a “subtle journey” from prescription-drug use to abuse
By Michelle Brandt on September 2nd, 2014
Watch: The judge and expert witnesses discuss new HCV regimens under development with or without ribavirin in this light-hearted innovative presentation.
By Lucinda K. Porter, RN
If you are thinking about delaying hepatitis C treatment, consider this: a review of mortality data found that those with hepatitis B or C die an average of 22 to 23 years earlier than those who don't have viral hepatitis...
If you are thinking about delaying hepatitis C treatment, consider this: a review of mortality data found that those with hepatitis B or C die an average of 22 to 23 years earlier than those who don't have viral hepatitis...
Al D. Rodriguez Liver Foundation
If only our livers could complain the way our stomachs grumble when we miss a meal during a hectic day at the office, perhaps many cases of liver cancer could be prevented. But alas, our livers don’t talk to us…. like that anyway
Sharing My Personal Experiences With Hepatitis C Treatment (Part II)
Fast forwarding 7 years later, and the drug Sovaldi was approved by the FDA in December 2013. By January 21st, 2014 I was on treatment with the new drug, and in just 4 weeks my Hepatitis C was gone! Not only was I a rapid responder to the new drug, but I remained undetected for the duration of my 24 weeks to July 7th...
Lastest Post - July
Finished. The Waiting Begins
If only our livers could complain the way our stomachs grumble when we miss a meal during a hectic day at the office, perhaps many cases of liver cancer could be prevented. But alas, our livers don’t talk to us…. like that anyway
Sharing My Personal Experiences With Hepatitis C Treatment (Part II)
By Andrew Styles
My name is Andrew Styles and I have Hepatitis C. Hepatitis C is a liver infection caused by a virus. Hepatitis means inflammation of the liver, an organ that carries out over 500 functions that keep you healthy. I just successfully completed a new treatment for Hepatitis C (Hep C) and want to inspire others to get tested and treated. I was treated in the past with serious side effects, but this time was different....
***Read Part I of my story at http://blog.mountsinai.org/blog/hepatitisc-treatment
***Read Part I of my story at http://blog.mountsinai.org/blog/hepatitisc-treatment
By Connie
The old adage ‘you are what you eat’ is true. What we eat affects our entire body, especially our liver. The liver is the powerhouse of the body. It is the second largest organ and helps with many vital functions. When our liver is unhealthy, it affects our entire body, even your immune system, which helps you fight disease.....
7 Weeks Post Treatment
By Joe Burke7 Weeks Post Treatment
Fast forwarding 7 years later, and the drug Sovaldi was approved by the FDA in December 2013. By January 21st, 2014 I was on treatment with the new drug, and in just 4 weeks my Hepatitis C was gone! Not only was I a rapid responder to the new drug, but I remained undetected for the duration of my 24 weeks to July 7th...
Lastest Post - July
By Don
This morning I downed my last $1800 worth of pills, tossed out the empty pill container, and began the worst part. Waiting. The gold standard is a three month test, October 23, if anyone is counting. The silver standard is …
Research
New Index Helps Predict Course of Early HCV Cirrhosis
By Lorraine L. Janeczko September 04, 2014
NEW YORK (Reuters Health) - A genomic signature, combined with bilirubin and platelet tests, can help identify patients with early hepatitis C virus (HCV) cirrhosis who are at high risk for complications, new research suggests.
"This study provides additional evidence that a gene signature . . . can itself predict future clinical events for a patient with HVC-related cirrhosis. It helps predict downstream deterioration in terms of liver failure and deaths from liver failure or risk for hepatocellular carcinoma," said co-senior author Dr. Raymond T. Chung of Harvard Medical School in Boston, in a phone call with Reuters Health.
"The most important aspect of this is really to help stratify or identify patients who may need more intensive follow-up, but also to potentially identify candidates for possible interventions that might help slow the progression of liver disease. Our hope would be to apply this in patients with a longer run-up so they can be identified further in advance and potentially intervened and treated before complications occur," he said.
Could this test replace the MELD the score?
"No," Dr. Chung said. "The MELD score presupposes that these patients already have advanced disease. The MELD in anybody who doesn't have cirrhosis should be in the normal range. It's only when cirrhosis has deteriorated that the MELD score starts to rise. We would intend this index to be used well before one ever had to use a MELD score."
As reported online August 20 in Gut, the components of the new prognostic index are a digital transcript counting assay (NanoString nCounter) consisting of a 186-gene signature, the bilirubin level (>1 mg/dL), and the platelet count (<100,000/mm3).
In an independent training group of 216 Italian patients with HCV cirrhosis followed for a median of 10 years, the prognostic index was associated with hepatic decompensation (hazard ratio=2.71, p=0.003), death (HR=6.00, p<0.001), hepatocellular carcinoma (HR=3.31, p=0.001) and progression of Child-Turcotte-Pugh class (HR=6.70, p<0.001).
The validation group consisted of 145 adults with compensated HCV cirrhosis who had liver biopsies over a 17-year period. Based on the prognostic index, the researchers stratified patients into groups at high-risk (16%), intermediate-risk (42%) or low-risk (42%).
The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), death (HR=3.57, p=0.002), liver-related death (HR=6.49, p<0.001) and all liver-related adverse events (HR=4.98, p<0.001).
Co-senior author Dr. Yujin Hoshida of the Icahn School of Medicine at Mount Sinai in New York City wrote in an email, "Our prognostic index was strikingly predictive of a series of hepatitis C cirrhosis complications with hazard ratios as high as 7.36. The magnitude of association is outstanding compared with previously reported molecular prognostic markers (with hazard ratios generally below 2.0). It's kind of surprising that we keep seeing the high prognostic association across multiple patient cohorts and assay platforms."
"The gene signature could be assayed on archived fixed liver biopsy tissues. You could do this by using daily clinical specimens without any special preparation. We have some preliminary data indicating that the gene signature is prognostic also in hepatitis B virus and nonalcoholic steatohepatitis (NASH). We're now analyzing these etiologies and as well as alcohol on a larger scale with National Institutes of Health support," he added.
Several of the authors are named investigators on a pending patent application involving compositions, kits, and methods for detecting, characterizing, preventing, and treating hepatic disorders. NanoString has secured the option to an exclusive worldwide license, but has no role in the current study.
SOURCE
New Index Helps Predict Course of Early HCV Cirrhosis
By Lorraine L. Janeczko September 04, 2014
NEW YORK (Reuters Health) - A genomic signature, combined with bilirubin and platelet tests, can help identify patients with early hepatitis C virus (HCV) cirrhosis who are at high risk for complications, new research suggests.
"This study provides additional evidence that a gene signature . . . can itself predict future clinical events for a patient with HVC-related cirrhosis. It helps predict downstream deterioration in terms of liver failure and deaths from liver failure or risk for hepatocellular carcinoma," said co-senior author Dr. Raymond T. Chung of Harvard Medical School in Boston, in a phone call with Reuters Health.
"The most important aspect of this is really to help stratify or identify patients who may need more intensive follow-up, but also to potentially identify candidates for possible interventions that might help slow the progression of liver disease. Our hope would be to apply this in patients with a longer run-up so they can be identified further in advance and potentially intervened and treated before complications occur," he said.
Could this test replace the MELD the score?
"No," Dr. Chung said. "The MELD score presupposes that these patients already have advanced disease. The MELD in anybody who doesn't have cirrhosis should be in the normal range. It's only when cirrhosis has deteriorated that the MELD score starts to rise. We would intend this index to be used well before one ever had to use a MELD score."
As reported online August 20 in Gut, the components of the new prognostic index are a digital transcript counting assay (NanoString nCounter) consisting of a 186-gene signature, the bilirubin level (>1 mg/dL), and the platelet count (<100,000/mm3).
In an independent training group of 216 Italian patients with HCV cirrhosis followed for a median of 10 years, the prognostic index was associated with hepatic decompensation (hazard ratio=2.71, p=0.003), death (HR=6.00, p<0.001), hepatocellular carcinoma (HR=3.31, p=0.001) and progression of Child-Turcotte-Pugh class (HR=6.70, p<0.001).
The validation group consisted of 145 adults with compensated HCV cirrhosis who had liver biopsies over a 17-year period. Based on the prognostic index, the researchers stratified patients into groups at high-risk (16%), intermediate-risk (42%) or low-risk (42%).
The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), death (HR=3.57, p=0.002), liver-related death (HR=6.49, p<0.001) and all liver-related adverse events (HR=4.98, p<0.001).
Co-senior author Dr. Yujin Hoshida of the Icahn School of Medicine at Mount Sinai in New York City wrote in an email, "Our prognostic index was strikingly predictive of a series of hepatitis C cirrhosis complications with hazard ratios as high as 7.36. The magnitude of association is outstanding compared with previously reported molecular prognostic markers (with hazard ratios generally below 2.0). It's kind of surprising that we keep seeing the high prognostic association across multiple patient cohorts and assay platforms."
"The gene signature could be assayed on archived fixed liver biopsy tissues. You could do this by using daily clinical specimens without any special preparation. We have some preliminary data indicating that the gene signature is prognostic also in hepatitis B virus and nonalcoholic steatohepatitis (NASH). We're now analyzing these etiologies and as well as alcohol on a larger scale with National Institutes of Health support," he added.
Several of the authors are named investigators on a pending patent application involving compositions, kits, and methods for detecting, characterizing, preventing, and treating hepatic disorders. NanoString has secured the option to an exclusive worldwide license, but has no role in the current study.
SOURCE
The most cost-effective strategy to determine treatment for patients with hepatitis C virus infection in the United Kingdom was to treat all patients regardless of fibrosis stage, according to new study data.
Specific serotonin reuptake inhibitors prevent interferon-α–induced depression in patients with Hepatitis C, reports the latest issue of the Clinical Gastroenterology & Hepatology.
Interferon-α (IFN-α)–induced depression is a major complication to treatment of chronic hepatitis C virus (HCV) infection.
Specific serotonin reuptake inhibitors (SSRIs) can be used to treat depression, but it is not clear whether they can prevent depression in patients receiving IFN therapy for chronic HCV infection.
Dr Bing Ruan and colleagues performed a meta-analysis by searching the Cochrane Library, PubMed, and EMBASE databases through 2013 for published results from randomized, placebo-controlled trials evaluating the utility of SSRIs in preventing IFN-induced depression in HCV patients.
The researchers analyzed data from 7 studies with a total of 662 patients.
The incidence of IFN-induced major depression and depression severity were defined as primary outcomes.
Sustained virologic response, completion of antiviral therapy, and tolerability were considered secondary outcomes.
A meta-analysis of IFN-induced major depression revealed that prophylactic SSRIs reduced the risk of depression, compared with placebo.
Proportions of patients achieving a sustained virologic response and completing antiviral therapy were similar between patients given SSRIs and controls.
The team noted that prophylactic SSRIs were tolerated in patients with HCV during treatment.
Dr Ruan's team comments, "On the basis of a meta-analysis of 7 randomized controlled trials, prophylactic administration of SSRIs to patients with HCV significantly lowered the incidence of IFN-induced major depression, compared with placebo, and the SSRIs were well tolerated."
Clin Gastroenterol Hepatol 2014: 12(9): 1452–1460.e3
02 September 2014
NATAP
Racial Differences in the Progression to Cirrhosis and Hepatocellular Carcinoma in HCV-Infected Veterans....."Hispanics with HCV had a 28 and 61% increased risk of developing both cirrhosis and HCC"
In this large US cohort of patients with HCV, we found that patients' race/ethnicity was independently associated with the risk of having cirrhosis and HCC recorded during follow-up. Specifically, we found that, compared with NHW patients with HCV, the odds of AAs being less likely to develop cirrhosis and HCC were 0.42 and 0.23, respectively. In contrast, Hispanics with HCV had a 28 and 61% increased risk of developing both cirrhosis and HCC, respectively, compared with NHWs. The effect of race persisted after we adjusted for confounders in the multivariable regression analyses and was consistent across several subgroups based on age, HCV genotype, and diabetes.
Marijuana use in hepatitis C infection does not affect liver biopsy histology or treatment outcomes.
Marijuana use was not associated with premature interruption of therapy for side effects, the likelihood of completing a full course of therapy or sustained virological response.
CONCLUSION: Marijuana use did not influence biopsy histology or alter key hard outcomes of hepatitis C virus antiviral therapy
Fatigue during treatment for hepatitis C virus: results of self-reported fatigue severity in two Phase IIb studies of simeprevir treatment in patients with hepatitis C virus genotype 1 infection
Next-generation sequencing sheds light on the natural history of hepatitis C infection in patients who fail treatment
In conclusion, deep sequencing technologies are a powerful tool for obtaining a more accurate insight into the dynamics of variants in the HCV quasispecies in human samples. The detection of multiple genotypes that have the potential to emerge following treatment may also have implications in the new era of DAAs when the presence of multiple genotypes and low-level resistance mutations may impact on treatment success.
Interferon-α (IFN-α)–induced depression is a major complication to treatment of chronic hepatitis C virus (HCV) infection.
Specific serotonin reuptake inhibitors (SSRIs) can be used to treat depression, but it is not clear whether they can prevent depression in patients receiving IFN therapy for chronic HCV infection.
Dr Bing Ruan and colleagues performed a meta-analysis by searching the Cochrane Library, PubMed, and EMBASE databases through 2013 for published results from randomized, placebo-controlled trials evaluating the utility of SSRIs in preventing IFN-induced depression in HCV patients.
The researchers analyzed data from 7 studies with a total of 662 patients.
The incidence of IFN-induced major depression and depression severity were defined as primary outcomes.
Sustained virologic response, completion of antiviral therapy, and tolerability were considered secondary outcomes.
A meta-analysis of IFN-induced major depression revealed that prophylactic SSRIs reduced the risk of depression, compared with placebo.
Proportions of patients achieving a sustained virologic response and completing antiviral therapy were similar between patients given SSRIs and controls.
The team noted that prophylactic SSRIs were tolerated in patients with HCV during treatment.
Dr Ruan's team comments, "On the basis of a meta-analysis of 7 randomized controlled trials, prophylactic administration of SSRIs to patients with HCV significantly lowered the incidence of IFN-induced major depression, compared with placebo, and the SSRIs were well tolerated."
Clin Gastroenterol Hepatol 2014: 12(9): 1452–1460.e302 September 2014
NATAP
Racial Differences in the Progression to Cirrhosis and Hepatocellular Carcinoma in HCV-Infected Veterans....."Hispanics with HCV had a 28 and 61% increased risk of developing both cirrhosis and HCC"
In this large US cohort of patients with HCV, we found that patients' race/ethnicity was independently associated with the risk of having cirrhosis and HCC recorded during follow-up. Specifically, we found that, compared with NHW patients with HCV, the odds of AAs being less likely to develop cirrhosis and HCC were 0.42 and 0.23, respectively. In contrast, Hispanics with HCV had a 28 and 61% increased risk of developing both cirrhosis and HCC, respectively, compared with NHWs. The effect of race persisted after we adjusted for confounders in the multivariable regression analyses and was consistent across several subgroups based on age, HCV genotype, and diabetes.
Marijuana use in hepatitis C infection does not affect liver biopsy histology or treatment outcomes.
Marijuana use was not associated with premature interruption of therapy for side effects, the likelihood of completing a full course of therapy or sustained virological response.
CONCLUSION: Marijuana use did not influence biopsy histology or alter key hard outcomes of hepatitis C virus antiviral therapy
Fatigue during treatment for hepatitis C virus: results of self-reported fatigue severity in two Phase IIb studies of simeprevir treatment in patients with hepatitis C virus genotype 1 infection
Next-generation sequencing sheds light on the natural history of hepatitis C infection in patients who fail treatment
In conclusion, deep sequencing technologies are a powerful tool for obtaining a more accurate insight into the dynamics of variants in the HCV quasispecies in human samples. The detection of multiple genotypes that have the potential to emerge following treatment may also have implications in the new era of DAAs when the presence of multiple genotypes and low-level resistance mutations may impact on treatment success.
Screening for Hepatocellular Carcinoma in Chronic Liver Disease: A Systematic Review Screening for Hepatocellular Carcinoma in Chronic Liver Disease
AASLD
Drs. Stephen A. Harrison and Robert J. Wong discuss the paper:
Nonalcoholic Steatohepatitis is the Most Rapidly Growing Indication for Liver Transplantation in Patients with Hepatocellular Carcinoma in the U.S..
AASLD
Drs. Stephen A. Harrison and Robert J. Wong discuss the paper:
Nonalcoholic Steatohepatitis is the Most Rapidly Growing Indication for Liver Transplantation in Patients with Hepatocellular Carcinoma in the U.S..
Related Link
HCV Weekend Reading: Fatty Liver Disease
HCV Weekend Reading: Fatty Liver Disease
Liver International, September 5, 2014
These are exciting times in the field of hepatitis C virus (HCV) infection. After many years of ominous predictions, the outlook for HCV-infected patients has improved substantially with the introduction of direct-acting agents.[1,2] However, it is too soon to declare victory. It has even been said that we are only 'at the end of the beginning' of the struggle.[3] There are several remaining obstacles. The purpose of this paper is to enumerate and discuss some of the remaining barriers to effective HCV treatment in the United States, predominantly from an inner city perspective.
NATAP
SVR Rates: predictors/liver disease stage(cirrhosis) - Abbvie 3D, Gilead's LDV/SOF, JNJ's SIM/SOF
This report takes a look at cirrhosis as a predictor of SVR response, considering 12 vs 24 weeks, addition or not of Rbv in the SOF/LDV studies, or in SIM/SOF studies although the numbers of patients in the SIM/SOF studies is small.
Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for Sofosbuvir
SVR Rates: predictors/liver disease stage(cirrhosis) - Abbvie 3D, Gilead's LDV/SOF, JNJ's SIM/SOF
This report takes a look at cirrhosis as a predictor of SVR response, considering 12 vs 24 weeks, addition or not of Rbv in the SOF/LDV studies, or in SIM/SOF studies although the numbers of patients in the SIM/SOF studies is small.
Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for Sofosbuvir
Data suggests that Sofosbuvir (SOF) has a high barrier to resistance; however, low frequency NS5B substitutions associated with treatment failure were identified that may contribute to resistance of this important drug for chronic hepatitis C virus (HCV) infection.
Clinical and Systematic Review
Clinical and Systematic Review
The Rapid Evolution of Treatment Strategies for Hepatitis C
Hepatitis C virus (HCV) treatment took a major step forward at the end of 2013 with the approvals of the second-generation protease inhibitor simeprevir (Olysio) and the nucleotide polymerase inhibitor sofosbuvir (Sovaldi). The interferon-free regimen of sofosbuvir and ribavirin is now available for genotype 2 and 3 patients. This regimen for 12 weeks is highly effective for genotype 2, whereas genotype 3 has proven to be more challenging and requires 24 weeks of therapy. Genotype 1 patients have reduced exposure to peginterferon-α with a 12-week regimen with sofosbuvir and a 24-week regimen with simeprevir. Genotype 4, 5, and 6 patients also respond well to the regimen of sofosbuvir, peginterferon-α, and ribavirin. In another landmark event, the initial approval of sofosbuvir included HCV/HIV-1 coinfected patients. Simeprevir and sofosbuvir also provide a window to the future with sustained virologic response (SVR) rates of >90% for genotype 1 when these agents are combined. Interferon-free regimens for genotype 1 patients have anticipated approvals in late 2014 or early 2015. Clinicians and patients will have the opportunity to discuss and select from current treatment options or await upcoming regimens. These potent new agents provide the tools to cure HCV for many patients.
Of Interest - In The News
We Now Have the Cure for Hepatitis C, but Can We Afford It?
A long, difficult and costly research effort gives doctors a new cure for hepatitis C
Aug 19, 2014 |By Jessica Wapner
A decades-long search for better treatments for a debilitating liver disorder is finally coming to fruition. Later this year the U.S. Food and Drug Administration is expected to approve a new pill that can cure hepatitis C—a chronic infection that afflicts about 170 million people worldwide and annually kills 350,000 people, including 15,000 in the U.S.—faster and with fewer side effects than current remedies.
The breakthrough treatment comes, however, at a price that may place it out of reach for all but the wealthiest or best-insured patients. It will contain two drugs, one of which is already available at $1,000 per dose, or $84,000 for a complete 12-week course. The dual-drug combination will likely cost even more, which has prompted outrage from physicians and patient advocates alike, as well as plans from insurers to ration the combination when it becomes commercially available.
Over the coming months, physicians, patients, economists and insurance companies will no doubt hotly debate whether the treatment is worth the full asking price. There is little doubt, however, that the medication's effectiveness is unprecedented and that its development is a significant achievement. A closer look at the complex chemical problems that needed to be solved to develop the cure shows why.
Fast and Invisible
Cures sometimes result from happy accidents—think penicillin mold growing in an overlooked petri dish. More often they require years of research into what is causing the problem in the first place. Understanding the science behind the new hepatitis C treatment starts with deciphering the meaning of the virus's name.
“Hepatitis” is a general term that refers to severe swelling or inflammation of the liver in response to certain drugs, toxins, excessive alcohol or infections—whether from bacteria or viruses. The letter C refers to the third in a series of viruses that researchers have isolated that specifically target and damage the liver. By the mid-1970s investigators had developed blood tests to identify hepatitis A, which typically spreads when infected individuals improperly handle food or water, and hepatitis B, which is often transmitted during sexual intercourse, the sharing of needles or contact with contaminated blood.
Soon after, researchers realized that a third form of viral hepatitis was silently spreading around the globe and that it was more likely than hepatitis A or B to result in permanent liver damage. By 1989 they had identified the virus that caused the condition. They also determined that the virus's genes mutate very fast—a process that has generated several equally successful varieties, called genotypes, and rendered an effective vaccine impossible to create so far. Hepatitis B virus, in contrast, does not evolve as quickly, and a vaccine against it has been available since the 1980s. Infection with hepatitis A virus, which usually causes symptoms within days, can also be prevented with a vaccine.
Standard treatment for hepatitis C has long been a synthetic, injectable version of interferon, one of the immune system's most powerful proteins, plus the antiviral drug ribavirin. The combination helps 25 to 75 percent of patients, depending on the genotype of the virus. But the side effects, including severe flulike symptoms, fatigue, depression and anemia, are often intolerable. In addition, the virus often becomes resistant to medication, allowing the disease to worsen.
Toward a Cure
Developing effective treatments against the virus required researchers to understand the structure of the various proteins that formed its outer shell, as well as the precise sequence of its genetic material, which is made up of RNA—a process that took the better part of the 1990s and involved researchers working around the globe in government, academia and industry.
With this information in hand, scientists still faced a long and costly phase of trial and error. They chose what looked like a promising target for treatment: an enzyme known as a protease that the virus depends on to make copies of itself. After several false starts, researchers at Vertex Pharmaceuticals, in collaboration with others, developed a protease inhibitor known as telaprevir, while scientists at Schering-Plough (which merged with Merck in 2009), created one called boceprevir. In clinical trials, 60 to 75 percent of patients receiving the standard treatment—ribavirin and interferon—as well as the two new drugs had no detectable signs of the virus in their bloodstream, compared with 44 percent or fewer patients receiving the typical treatment alone.
The FDA approved the new drugs in 2011, but the sense of triumph felt by many in the medical community soon gave way to disappointment. The medications had harsh side effects and worked only for those patients with a particular genetic variant of the virus known as genotype 1, which is the most common type in the U.S. and Canada but rare in many other countries with hepatitis C epidemics. Moreover, the continued need for interferon and ribavirin, with their attendant side effects, was a huge drawback.
As enthusiasm for telaprevir and boceprevir waned, other viral proteins emerged as promising drug targets. What scientists had learned from their earlier research, however, was that inactivating an enzyme or protein was not enough. To stop hepatitis C, any effective drug also had to incorporate itself into the virus's genetic code, where it would need to halt the virus's ability to make new copies of its genes and thus to make new virus. In addition, to avoid potentially debilitating side effects, the medication had to get to the liver quickly and directly, bypassing as many other organs as possible.
A company called Pharmasset had been looking at a group of drugs known as nucleotide analogues, which met some of these criteria, since the mid-2000s. Constructed by stitching molecules that resemble the building blocks of DNA and RNA with a molecule made of phosphorus plus oxygen (known as a phosphate), these compounds inserted themselves into the virus's genes, where they promptly fell apart, interfering with viral replication.
Researchers then ran into a few big biochemical problems. Because the nucleotide analogues were water-soluble, they could not traverse the fatty lining of the intestine (fats and water do not mix) to reach the bloodstream and then the liver. In addition, the phosphate group carried a double negative electrical charge, further restricting its ability to move across the intestine's electrically neutral membrane. Finally, other enzymes in the liver easily dislodged the phosphate group from the nucleotide analogue, rendering the compound ineffective.
Michael Sofia, then at Pharmasset, solved the problems by adding two compounds known as esters to the analogue. This addition both shielded the negative charges and made the drug greasy, enabling it to leave the gut. Once inside liver cells, the enzymes that had initially interfered with the phosphate group hit the ester molecules instead, leaving the active drug free to do its job. The new formulation was named sofosbuvir in Sofia's honor; the company was purchased, in 2011, by Gilead for $11 billion.
In a large study, 295 out of 327 patients treated with sofosbuvir, as well as ribavirin and interferon, showed no signs of the virus in their blood after 12 weeks. In a more advanced trial, 12 weeks of sofosbuvir plus ribavirin yielded the same results as 24 weeks of interferon plus ribavirin: 67 percent of patients had no evidence of the virus in their blood (although side effects such as fever and depression were fewer among patients who did not receive interferon). The FDA approved sofosbuvir in late 2013 as a treatment for hepatitis C in combination with ribavirin.
Still, investigators pushed to make further improvements. During sofosbuvir's development, they had studied other drugs that inhibited different viral proteins and that might eliminate the need for continued use of interferon and ribavirin. So they ran another study of sofosbuvir plus one such complementary drug, daclatasvir, made by Bristol-Myers Squibb. The result: nearly all patients were cured of the disease, with far fewer side effects than before. Since then, Gilead has run three additional studies of sofosbuvir paired with a different drug, ledipasvir. The combination cured at least 94 percent of patients with genotype 1 disease.
It is this combination, mixed in a single daily pill, that industry watchers expect the FDA to approve by October 2014. It heralds a new era of curative treatment for patients with hepatitis C. Similar drugs that work equally well for all genotypes are now in the final stages of clinical development.
Financial Resistance
Because the soon to be released combination pill cures hepatitis in just 12 weeks—eliminating the need for and the expense of treating an otherwise chronic illness—it may end up costing less overall than previous treatments. (Gilead is not expected to announce the retail price of the pill until it receives FDA approval.) Of course, that does not mean that patients will be to afford it.
David Thomas, director of the division of infectious diseases at Johns Hopkins University, considers the price an impediment to health care around the globe, despite the potential savings. Many people in the U.S. with hepatitis C are poor, and several hundred thousand are incarcerated. “Medication that costs more than $100,000 won't make a big impact in prisons in Russia or for drug users in Pakistan,” Thomas says. Within the U.S., copayments may put the treatment out of reach.
The price tag has also struck a nerve among insurers and other third-party payers. “We've never had such a high-cost drug for such a large population,” says Brian Henry, a spokesperson at Express Scripts, which manages benefits for more than 3,500 companies. “Treatment for one hepatitis C patient now can take up a huge portion of a small business's budget for drug spending.”
The manufacturer insists that cost will not prevent access. As it has for its HIV drugs, Gilead plans to provide patient assistance within the U.S., to license the drug (for a fee) to select generic manufacturers outside the U.S., and to lower prices in low- and middle-income countries. In Egypt, which has the world's highest rate of hepatitis C, sofosbuvir costs $300 for a 28-day supply.
At the FDA meeting to review sofosbuvir for approval, Sofia listened to testimony from a patient who had been cured by the new drugs at practically the last minute. “Stories like this,” Sofia says, “put everything one does in perspective.” How many other patients get to tell such stories remains to be seen.
Hepatitis C virus (HCV) treatment took a major step forward at the end of 2013 with the approvals of the second-generation protease inhibitor simeprevir (Olysio) and the nucleotide polymerase inhibitor sofosbuvir (Sovaldi). The interferon-free regimen of sofosbuvir and ribavirin is now available for genotype 2 and 3 patients. This regimen for 12 weeks is highly effective for genotype 2, whereas genotype 3 has proven to be more challenging and requires 24 weeks of therapy. Genotype 1 patients have reduced exposure to peginterferon-α with a 12-week regimen with sofosbuvir and a 24-week regimen with simeprevir. Genotype 4, 5, and 6 patients also respond well to the regimen of sofosbuvir, peginterferon-α, and ribavirin. In another landmark event, the initial approval of sofosbuvir included HCV/HIV-1 coinfected patients. Simeprevir and sofosbuvir also provide a window to the future with sustained virologic response (SVR) rates of >90% for genotype 1 when these agents are combined. Interferon-free regimens for genotype 1 patients have anticipated approvals in late 2014 or early 2015. Clinicians and patients will have the opportunity to discuss and select from current treatment options or await upcoming regimens. These potent new agents provide the tools to cure HCV for many patients.
Of Interest - In The News
We Now Have the Cure for Hepatitis C, but Can We Afford It?
A long, difficult and costly research effort gives doctors a new cure for hepatitis C
Aug 19, 2014 |By Jessica Wapner
A decades-long search for better treatments for a debilitating liver disorder is finally coming to fruition. Later this year the U.S. Food and Drug Administration is expected to approve a new pill that can cure hepatitis C—a chronic infection that afflicts about 170 million people worldwide and annually kills 350,000 people, including 15,000 in the U.S.—faster and with fewer side effects than current remedies.
The breakthrough treatment comes, however, at a price that may place it out of reach for all but the wealthiest or best-insured patients. It will contain two drugs, one of which is already available at $1,000 per dose, or $84,000 for a complete 12-week course. The dual-drug combination will likely cost even more, which has prompted outrage from physicians and patient advocates alike, as well as plans from insurers to ration the combination when it becomes commercially available.
Over the coming months, physicians, patients, economists and insurance companies will no doubt hotly debate whether the treatment is worth the full asking price. There is little doubt, however, that the medication's effectiveness is unprecedented and that its development is a significant achievement. A closer look at the complex chemical problems that needed to be solved to develop the cure shows why.
Fast and Invisible
Cures sometimes result from happy accidents—think penicillin mold growing in an overlooked petri dish. More often they require years of research into what is causing the problem in the first place. Understanding the science behind the new hepatitis C treatment starts with deciphering the meaning of the virus's name.
“Hepatitis” is a general term that refers to severe swelling or inflammation of the liver in response to certain drugs, toxins, excessive alcohol or infections—whether from bacteria or viruses. The letter C refers to the third in a series of viruses that researchers have isolated that specifically target and damage the liver. By the mid-1970s investigators had developed blood tests to identify hepatitis A, which typically spreads when infected individuals improperly handle food or water, and hepatitis B, which is often transmitted during sexual intercourse, the sharing of needles or contact with contaminated blood.
Soon after, researchers realized that a third form of viral hepatitis was silently spreading around the globe and that it was more likely than hepatitis A or B to result in permanent liver damage. By 1989 they had identified the virus that caused the condition. They also determined that the virus's genes mutate very fast—a process that has generated several equally successful varieties, called genotypes, and rendered an effective vaccine impossible to create so far. Hepatitis B virus, in contrast, does not evolve as quickly, and a vaccine against it has been available since the 1980s. Infection with hepatitis A virus, which usually causes symptoms within days, can also be prevented with a vaccine.
Standard treatment for hepatitis C has long been a synthetic, injectable version of interferon, one of the immune system's most powerful proteins, plus the antiviral drug ribavirin. The combination helps 25 to 75 percent of patients, depending on the genotype of the virus. But the side effects, including severe flulike symptoms, fatigue, depression and anemia, are often intolerable. In addition, the virus often becomes resistant to medication, allowing the disease to worsen.
Toward a Cure
Developing effective treatments against the virus required researchers to understand the structure of the various proteins that formed its outer shell, as well as the precise sequence of its genetic material, which is made up of RNA—a process that took the better part of the 1990s and involved researchers working around the globe in government, academia and industry.
With this information in hand, scientists still faced a long and costly phase of trial and error. They chose what looked like a promising target for treatment: an enzyme known as a protease that the virus depends on to make copies of itself. After several false starts, researchers at Vertex Pharmaceuticals, in collaboration with others, developed a protease inhibitor known as telaprevir, while scientists at Schering-Plough (which merged with Merck in 2009), created one called boceprevir. In clinical trials, 60 to 75 percent of patients receiving the standard treatment—ribavirin and interferon—as well as the two new drugs had no detectable signs of the virus in their bloodstream, compared with 44 percent or fewer patients receiving the typical treatment alone.
The FDA approved the new drugs in 2011, but the sense of triumph felt by many in the medical community soon gave way to disappointment. The medications had harsh side effects and worked only for those patients with a particular genetic variant of the virus known as genotype 1, which is the most common type in the U.S. and Canada but rare in many other countries with hepatitis C epidemics. Moreover, the continued need for interferon and ribavirin, with their attendant side effects, was a huge drawback.
As enthusiasm for telaprevir and boceprevir waned, other viral proteins emerged as promising drug targets. What scientists had learned from their earlier research, however, was that inactivating an enzyme or protein was not enough. To stop hepatitis C, any effective drug also had to incorporate itself into the virus's genetic code, where it would need to halt the virus's ability to make new copies of its genes and thus to make new virus. In addition, to avoid potentially debilitating side effects, the medication had to get to the liver quickly and directly, bypassing as many other organs as possible.
A company called Pharmasset had been looking at a group of drugs known as nucleotide analogues, which met some of these criteria, since the mid-2000s. Constructed by stitching molecules that resemble the building blocks of DNA and RNA with a molecule made of phosphorus plus oxygen (known as a phosphate), these compounds inserted themselves into the virus's genes, where they promptly fell apart, interfering with viral replication.
Researchers then ran into a few big biochemical problems. Because the nucleotide analogues were water-soluble, they could not traverse the fatty lining of the intestine (fats and water do not mix) to reach the bloodstream and then the liver. In addition, the phosphate group carried a double negative electrical charge, further restricting its ability to move across the intestine's electrically neutral membrane. Finally, other enzymes in the liver easily dislodged the phosphate group from the nucleotide analogue, rendering the compound ineffective.
Michael Sofia, then at Pharmasset, solved the problems by adding two compounds known as esters to the analogue. This addition both shielded the negative charges and made the drug greasy, enabling it to leave the gut. Once inside liver cells, the enzymes that had initially interfered with the phosphate group hit the ester molecules instead, leaving the active drug free to do its job. The new formulation was named sofosbuvir in Sofia's honor; the company was purchased, in 2011, by Gilead for $11 billion.
In a large study, 295 out of 327 patients treated with sofosbuvir, as well as ribavirin and interferon, showed no signs of the virus in their blood after 12 weeks. In a more advanced trial, 12 weeks of sofosbuvir plus ribavirin yielded the same results as 24 weeks of interferon plus ribavirin: 67 percent of patients had no evidence of the virus in their blood (although side effects such as fever and depression were fewer among patients who did not receive interferon). The FDA approved sofosbuvir in late 2013 as a treatment for hepatitis C in combination with ribavirin.
Still, investigators pushed to make further improvements. During sofosbuvir's development, they had studied other drugs that inhibited different viral proteins and that might eliminate the need for continued use of interferon and ribavirin. So they ran another study of sofosbuvir plus one such complementary drug, daclatasvir, made by Bristol-Myers Squibb. The result: nearly all patients were cured of the disease, with far fewer side effects than before. Since then, Gilead has run three additional studies of sofosbuvir paired with a different drug, ledipasvir. The combination cured at least 94 percent of patients with genotype 1 disease.
It is this combination, mixed in a single daily pill, that industry watchers expect the FDA to approve by October 2014. It heralds a new era of curative treatment for patients with hepatitis C. Similar drugs that work equally well for all genotypes are now in the final stages of clinical development.
Financial Resistance
Because the soon to be released combination pill cures hepatitis in just 12 weeks—eliminating the need for and the expense of treating an otherwise chronic illness—it may end up costing less overall than previous treatments. (Gilead is not expected to announce the retail price of the pill until it receives FDA approval.) Of course, that does not mean that patients will be to afford it.
David Thomas, director of the division of infectious diseases at Johns Hopkins University, considers the price an impediment to health care around the globe, despite the potential savings. Many people in the U.S. with hepatitis C are poor, and several hundred thousand are incarcerated. “Medication that costs more than $100,000 won't make a big impact in prisons in Russia or for drug users in Pakistan,” Thomas says. Within the U.S., copayments may put the treatment out of reach.
The price tag has also struck a nerve among insurers and other third-party payers. “We've never had such a high-cost drug for such a large population,” says Brian Henry, a spokesperson at Express Scripts, which manages benefits for more than 3,500 companies. “Treatment for one hepatitis C patient now can take up a huge portion of a small business's budget for drug spending.”
The manufacturer insists that cost will not prevent access. As it has for its HIV drugs, Gilead plans to provide patient assistance within the U.S., to license the drug (for a fee) to select generic manufacturers outside the U.S., and to lower prices in low- and middle-income countries. In Egypt, which has the world's highest rate of hepatitis C, sofosbuvir costs $300 for a 28-day supply.
At the FDA meeting to review sofosbuvir for approval, Sofia listened to testimony from a patient who had been cured by the new drugs at practically the last minute. “Stories like this,” Sofia says, “put everything one does in perspective.” How many other patients get to tell such stories remains to be seen.
This article was originally published with the title "The Solid-Gold Wonder Drug."
By Jen Christensen, CNN
updated 12:27 PM EDT, Wed September 3, 2014
(CNN) -- Dr. Sean Kumer is actually happy when a call from work wakes him from a deep sleep.
A call means the transplant surgeon at The University of Kansas Hospital can save another life. He worries, though, about possible changes being discussed regarding the way donated organs are distributed; if they go into effect, he may not be able to save so many lives.
"I worry (the possible changes) will harm my patients," Kumer said.
On September 16, the United Network for Organ Sharing, the nonprofit that manages the nation's transplant system, will hold a public hearing to discuss ways to "increase equity" in how organs are assigned to patients across the country. Each organ has a different system for handling its waiting list, and the network has seen a particular problem with donated livers....
updated 12:27 PM EDT, Wed September 3, 2014
(CNN) -- Dr. Sean Kumer is actually happy when a call from work wakes him from a deep sleep.
A call means the transplant surgeon at The University of Kansas Hospital can save another life. He worries, though, about possible changes being discussed regarding the way donated organs are distributed; if they go into effect, he may not be able to save so many lives.
"I worry (the possible changes) will harm my patients," Kumer said.
On September 16, the United Network for Organ Sharing, the nonprofit that manages the nation's transplant system, will hold a public hearing to discuss ways to "increase equity" in how organs are assigned to patients across the country. Each organ has a different system for handling its waiting list, and the network has seen a particular problem with donated livers....
Reuters Health Information
Increasing Rates of Acute Hepatitis C Infection Among Young Americans
By Will Boggs MD
September 03, 2014NEW YORK (Reuters Health) - The incidence of acute hepatitis C infection is rising rapidly among Americans aged 30 years and younger, especially those living in non-urban areas, according to U.S. data.
"Because our study revealed a strong relationship between new infections and injection drug use among youth, we would encourage providers to be on high alert for these risk behaviors in young patients," said senior author Dr. Scott D. Holmberg from the Centers for Disease Control and Prevention in Atlanta, Georgia.
"Assessing their risk can be an important opportunity -- not only for testing but also to provide appropriate therapy or referral to drug-cessation treatment," he told Reuters Health by email.
The number of acute cases of hepatitis C virus (HCV) infection had declined rapidly between 1992 and 2003. But since 2006, there has been a resurgence, especially among younger persons who inject drugs.
Between 2006 and 2012, the agency received reports of 7,169 cases of acute hepatitis C. Nearly half of all cases in 2012 involved people aged 30 years and younger, versus only 36% of cases in 2006, the researchers report in Clinical Infectious Diseases, online August 11.
Thirty of 34 states and territories reporting to CDC reported higher incidence of acute HCV in 2012 compared to 2006 among young persons. Fifteen percent of these states had increases between 100% and 199%, and 50% had increases of at least 200%.
In this age group, the incidence of reported acute HCV infection increased 13% per year in non-urban counties and 5% per year in urban counties. The greatest year-to-year increase occurred from 2010 to 2011, when the increase was 38% in non-urban and 85% in urban counties.
Supplemental case follow-up of 1,202 cases in six jurisdictions revealed that 77% of those newly infected had used injected drugs (57% of these shared needles or syringes and 82% shared other drug preparation equipment).
Among those interviewed, 84% reported having ever used drugs, including marijuana (91%), alcohol (83%), prescription opioids (76%), powder cocaine (71%) and heroin (61%). For the 54% who used both heroin and prescription opioids, heroin use followed the use of prescription opioids by an average 2.4 years.
The researchers note that these reports "grossly underestimate HCV incidence in young persons for many reasons, but mainly because most acute infections are asymptomatic and cannot be detected."
"A comprehensive approach is needed to address the increases in HCV infection among young persons," they conclude. "The early abuse of prescription opioids presents an opportunity to mitigate high-risk behaviors. Possible interventions include provider education to reduce opioid misuse, treatment of drug abuse and addiction, national prescription opioid monitoring, and aggressive early education to mitigate evolution to injection drug use."
"Currently, CDC is supporting demonstration projects in two rural and Appalachian settings to conduct outreach to young people who inject drugs," Dr. Holmberg said. "Our goal is to better understand how to identify these at-risk youth, as well as how to test and appropriately treat them."
"While we've recently seen great advances in hepatitis C treatment, including the availability of new treatments, these new therapies only work if people receive them," Dr. Holmberg said. "The potential of these and other advances depends on our ability to get more people screened and into care.""Testing, specifically, is the first critical step to stemming the toll of death and disease from hepatitis C in this nation," he added. "CDC recommends testing for those known to be at high risk, which includes anyone with a history of injection drug use (other key hepatitis C testing recommendations can be found at http://1.usa.gov/1B8Zj9d). "
Dr. Brian R. Edlin and Emily Winkelstein from the National Development and Research Institutes in New York, who were not involved in the study, recently published an article on the question of whether hepatitis C can be eradicated in the U.S.
"We're at a watershed in this disease now, with the opportunity to end the hepatitis C epidemic within our grasp, but there's a lot that needs to be done to take advantage of the opportunity," Dr. Edlin told Reuters Health by email. "A potentially fatal, lifelong blood-borne viral disease has gone from incurable to curable, which is a historic event in the history of medicine. But the way things are going, it will just move into the forgotten sectors of society, stay there, and continue to spread, until we make a concerted effort to eradicate it."
"Primary care doctors have a terrific opportunity," Dr. Edlin said. "They see patients before they wind up in the emergency room, or jail, or the morgue. Even better, they can organize outreach to young people at risk. Work with the health department, the police, churches and social services to reach out to young people at risk. As doctors, they have a special credibility that others don't. Express concern. Teach. Counsel. Test. And treat."
Winkelstein added, "While I am not a physician, I have heard countless stories from young people who use drugs who have been treated poorly once drug use is discovered or disclosed. More often than not, young people report that physicians shift their dialogue entirely from whatever brought the young person to the physician to a lecture about cessation of all drug use. As a result, young people either stop seeking medical care or don't disclose important health information to in order to avoid backlash."
"Physicians need to find a way to challenge drug-related stigma rather than reinforce it," Winkelstein said. "They must find ways to treat young people with compassion and empathy regardless of their choices around drug use, and seize the opportunity to build trust, provide meaningful education about ways to reduce their risk of getting or transmitting HCV and treat people who are already infected regardless of ongoing use. Physicians can use treatment as a way to continue engagement with young people and prevent reinfection."
Dr. Benjamin P. Linas from Boston University School of Public Health argued that it will be difficult for doctors to have a big impact because young drug users rarely go to the doctor.
"To really stop this spread of infection, we need to focus on substance abuse treatment," he told Reuters Health by email.
"There is a great deal of discussion about the new HCV meds and how we may be able to use them to eradicate HCV," said Dr. Linas, who was not involved in the study. "Maybe we can -- but treatment as prevention cannot work if kids are relapsing to injection drug use and becoming reinfected."
He added, "As a public health/medical community, we need to expand our thinking about HCV beyond the 'boomers.' It was important and appropriate to begin with the recommendation to screen the birth cohort, but it's time to move to the next phase and realize that if we want to really stop new infections, we need to do the very hard work of identifying and engaging HCV-infected active drug users in care, help them stop their drug use, and treat their HCV."
SOURCE
Clin Infect Dis 2014.
Stanford addiction expert: It’s often a “subtle journey” from prescription-drug use to abuse
By Michelle Brandt on September 2nd, 2014
Here are some frightening facts you might not know: Drug overdose death rates
in the United States have more than
tripled since 1990, with the majority of drug-related deaths caused by
prescription drugs. And as of 2010, about 18
women in the U.S. die every day of a prescription painkiller overdose.
Prescription-drug abuse, which we’ve written about extensively here on Scope, is
a very real and pressing issue – and it was the focus of a recent Forum on
KQED-FM.
Read more here...
Listen To The Program
Read more here...
Listen To The Program
See you all soon.....
Always Tina
Always Tina
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